The field of the invention is medical testing and the invention relates more particularly to screening the effect of chemotherapeutic agents in vivo using target cells grown in bio-compatible semi-permeable membrane capsules.
A method of evaluating chemotherapeutic agents in vivo is disclosed in U.S. Pat. No. 5,698,413 which is hereby incorporated by reference herein. The method broadly utilizes the encapsulation of target cells, such as tumors, or cells with viral infection within a small capsule, which capsule has a microporous wall. This capsule is then implanted in a living organism. The encapsulation prevents the spread of the tumor or other target cells from within the capsule into the living organism. Such target cells, being larger than the pores of the wall of the capsule, are unable to migrate therethrough to spread the tumor to the host. The pores in the capsule wall, however, are large enough to permit the permeation of the treatment into the interior of the capsule through the cell wall, since the treatment substances are smaller than the openings in the pores of the capsule wall. Then after the living organism has been subjected to appropriate treatment, the capsule is removed and the effect of the treatment on the tumor or other target cell within the capsule can be determined.
In order for the target cell to multiply, it has been found necessary, or at least highly desirable, that the cell be capable of becoming anchored to the inner wall of the capsule. On the other hand, it is undesirable for the outer wall of the capsule to anchor itself unduly to the host, since this makes it difficult to remove for evaluation.
The formulation, fabrication, application of hollow membrane structures are well known in the prior art. Such hollow membrane structures have been used for filtration, purification, and reclamation of industrial waste products. Such microporous members are also used in highly sophisticated bio-medical applications in the health services field. Typical applications include hemodialysis, extracorporeal gas exchange, process filtration of pharmaceutical solutions, and the cultivation and expansion of mammalian cells in bioreactors. Such hollow fiber membranes are most typically made by conventional synthetic fiber spinning methods to provide hollow fiber membrane structures. The spinning methods include melt spinning, dry spinning, wet spinnings, and various combinations thereof. These methods are well illustrated in the following U.S. Pat. Nos. 4,035,459; 4,127,625; 4,229,154; 4,322,381; 4,323,627; 4,342,711; 4,380,520; and 4,744,932.
Various human or animal tumor cell lines and HIV infiltrated cells have been successfully encapsulated and implanted in a host biological model as set forth in U.S. Pat. No. 5,698,413. Polymers used for such encapsulation include polysulfone, polyether sulfone, and polyvinyledene difloride. Unfortunately, the ideal properties for the inner wall of the encapsulation medium differ from the ideal properties desired from the outer wall. The inner wall requires a significant amount of cell adhesion, whereas too much cell adhesion is a disadvantage on the outer wall, since it interferes with the removal of the capsule after completion of the test. Conversely, to provide a polymer which can readily be removed can provide too little adhesion for the encouragement of cell proliferation within the capsule.
It is, thus, an object of the present invention to provide a hollow fiber membrane structure having an inner wall with optimum cell proliferation characteristics and an outer wall with optimum capsule removal characteristics.
The present invention is for a bi-component microporous hollow fiber member structure for use in the in vivo propagation of cells within the structure. The structure has a semi-permeable inner microporous structure fabricated from a microporous bio-compatible polymer, having a pore size of between 10 and 1000 Angstroms but preferably 10-200 Angstroms, and having the property of cell adhesion to the inner surface thereof. A semi-permeable outer porous structure covers the outer surface of the inner microporous structure, and is fabricated from a polymer having a lower tendency to permit cell adhesion than the polymer from which the inner microporous structure is fabricated. Preferred polymers for the inner microporous structure include polysulfone and polyether sulfone. Preferred polymers for the outer microporous structure are polyvinyledene difloride and polypropylene. Preferably, this bi-component structure is formed in a generally tubular shape and heat sealed at intervals to provide compartments containing media and living cells. The heat sealed compartment may then be implanted in a living organism and then used for various purposes, including evaluation of medical treatments.